Researchers at the University of Southampton have developed a promising new way to bolster the body’s immune system response to cancer.
They used specially engineered multi-pronged antibodies to better activate immune response to cancer-killing T cells.
The antibodies work by ‘grabbing’ and ‘clustering’ multiple immune cell receptors, thereby boosting the signal that tells the T cell to attack the cancer.
They did this by focusing on an immune receptor called CD27, which needs a matching key (ligand) to activate T cells. This ligand is produced naturally in response to infection, but cancers lack this signal and T cells can only elicit a weak response against the cancer cells.
Four-pronged antibodies revolutionise immune response
Antibodies can work a bit like a master key, but the most commonly used antibodies are Y-shaped molecules with two prongs, meaning they can engage only two receptors at the same time.
While antibodies have revolutionised cancer treatment, some cancers don’t respond because T cells don’t receive all the signals they need to become fully active.
The antibodies developed by the researchers have four prongs, allowing them to grab onto more receptors and improve the body’s immune response.
They also enlist the help of a second cell, forcing all the CD27 receptors they are holding to clump together. This amplifies the signal and mimics the body’s natural activation of CD27.
Professor Aymen Al‑Shamkhani at the University of Southampton, who led the study, explained: “We already understood how the body’s natural CD27 signal switches on T cells, but turning that knowledge into a medicine was the real challenge.
“Antibodies are reliable molecules that make excellent drugs. However, the natural antibody format was not powerful enough, so we had to create a more effective version.”
The new antibodies are more effective in targeting T cells
In lab studies using mice and human immune cells, the new antibodies were more effective at activating CD8⁺ T cells – the ‘special forces’ of the immune system – than standard Y-shaped antibodies, delivering a more robust anti-tumour response.
By making CD27 more responsive to therapeutic targeting, the findings provide a blueprint for developing next‑generation immunotherapies that harness the immune system to fight cancer more effectively.
Professor Al‑Shamkhani concluded: “This approach could help improve future cancer treatments by allowing the immune system to work closer to its full potential.”
